tbuckley/cabot-search huggingface dataset:
Redefining attrition in multiple myeloma (MM): a Canadian Myeloma Research Group (CMRG) analysis
Authors: Arleigh McCurdy, Hira Mian, Richard LeBlanc, Victor H. Jimenez-Zepeda, Jiandong Su, Esther Masih-Khan, Alissa Visram, Martha Louzada, Kevin Song, Darrell White, Michael Sebag, Julie Stakiw, Anthony Reiman, Muhammad Aslam, Debra Bergstrom, Rami Kotb, Rayan Kaedbey, Engin Gul, Donna Reece, Christopher P. Venner
Journal: Blood Cancer Journal (2023)

While most patients diagnosed with multiple myeloma (MM) receive initial therapy, reported attrition rates are high. Understanding attrition rates and characteristics of patients not receiving subsequent therapy is useful for MM stakeholders. We performed an analysis of attrition rates in a large disease-specific database of patients with newly diagnosed MM who received at least one line of therapy between Jan 1/10-Dec 31/20. Attrition was defined as failure to receive a subsequent line of therapy despite progression of MM or due to death. A total of 5548 patients were identified, 3111 autologous stem cell transplant (ASCT) patients and 2437 non-ASCT. In the ASCT cohort, the attrition rate was 7% after line 1, 12% after line 2, and 23% after line 3. In non-ASCT patients, the attrition rate was 19% after line 1, 26% after line 2, and 40% after line 3. Death was the dominant contributor to attrition across all cohorts, with a minority of patients alive with progressive disease in the absence of further therapy at each line. Multivariable analysis identified older age, shorter time to progression, and inferior response as independent risk factors for attrition. Our data show that attrition rates increase with each line of therapy and are higher in non-ASCT patients but are appreciably lower than previously reported. This study supports a revision of the previous definition of attrition, demonstrating that most patients who do not receive subsequent therapy are either continuing their current therapy and/or are in remission off-treatment rather than being irreversibly lost to attrition.
Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy
Authors: Tim H. H. Coorens, Grace Collord, Taryn D. Treger, Stuart Adams, Emily Mitchell, Barbara Newman, Gad Getz, Anna L. Godfrey, Jack Bartram, Sam Behjati
Journal: Nature Cancer (2023)

Abstract Children with acute lymphoblastic leukemia (ALL) undergoing anti-CD19 therapy occasionally develop acute myeloid leukemia (AML). The clonal origin of such lineage-switch leukemias 1–4 remains unresolved. Here, we reconstructed the phylogeny of multiple leukemias in a girl who, following multiply relapsed ALL, received anti-CD19 cellular and antibody treatment and subsequently developed AML. Whole genome sequencing unambiguously revealed the AML derived from the initial ALL, with distinct driver mutations that were detectable before emergence. Extensive prior diversification and subsequent clonal selection underpins this fatal lineage switch. Genomic monitoring of primary leukemias and recurrences may predict therapy resistance, especially regarding anti-CD19 treatment.
Targeted co-delivery of resiquimod and a SIRPα variant by liposomes to activate macrophage immune responses for tumor immunotherapy
Authors: Dianlong Jia, Yue Lu, Mingjia Lv, Feifei Wang, Xiaomeng Lu, Weifan Zhu, Jianmei Wei, Wen Guo, Renmin Liu, Guangyong Li, Rui Wang, Jun Li, Fengjiao Yuan
Journal: Journal of Controlled Release (2023)
Molecular Residual Disease in Breast Cancer: Detection and Therapeutic Interception
Authors: Arielle J. Medford, Beverly Moy, Laura M. Spring, Sara A. Hurvitz, Nicholas C. Turner, Aditya Bardia
Journal: Clinical Cancer Research (2023)

Abstract Breast cancer remains a leading cause of cancer-related death in women despite screening and therapeutic advances. Early detection allows for resection of local disease; however, patients can develop metastatic recurrences years after curative treatment. There is no reliable blood-based monitoring after curative therapy, and radiographic evaluation for metastatic disease is performed only in response to symptoms. Advances in circulating tumor DNA (ctDNA) assays have allowed for a potential option for blood-based monitoring. The detection of ctDNA in the absence of overt metastasis or recurrent disease indicates molecular evidence of cancer, defined as molecular residual disease (MRD). Multiple studies have shown that MRD detection is strongly associated with disease recurrence, with a lead time prior to clinical evidence of recurrence of many months. Importantly, it is still unclear whether treatment changes in response to ctDNA detection will improve outcomes. There are currently ongoing trials evaluating the efficacy of therapy escalation in the setting of MRD, and these studies are being conducted in all major breast cancer subtypes. Additional therapies under study include CDK4/6 inhibitors, PARP inhibitors, HER2-targeted therapies, and immunotherapy. This review will summarize the underlying scientific principles of various MRD assays, their known prognostic roles in early breast cancer, and the ongoing clinical trials assessing the efficacy of therapy escalation in the setting of MRD.
<i>JAMA Surgery</i> Reaffirmation to Diversity, Equity, and Inclusion
Authors: Lisa A. Newman, Leah M. Backhus, Melina R. Kibbe
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
CPAP therapy for obstructive sleep apnoea: persisting challenges in outcome assessment
Authors: Walter T. McNicholas, Erna Sif Arnardottir, Timo Leppänen, Sophia Schiza, Winfried Randerath
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>A government-sponsored US report that CPAP therapy for sleep apnoea did not benefit clinical outcomes is compromised by reliance on RCTs with inappropriate patient selection and failure to include evidence of benefit of CPAP on excessive daytime sleepiness</b>https://bit.ly/3G3drdu
A Ground’s-Eye View on Racial and Ethnic Disparities in Cancer Clinical Trial Participation
Authors: Joseph M. Unger
Journal: JAMA Network Open (2023)

Harlan Pittell, PhD; Gregory S. Calip, PharmD, MPH, PhD; Amy Pierre, MSN, ANP-BC; Cleo A. Ryals, PhD; Ivy Altomare, MD; Trevor J. Royce, MD, MS, MPH; Jenny S. Guadamuz, MSPH, PhD
Timing and Reporting of Secondary Overall Survival End Points for Phase III Trials in Advanced/Metastatic Disease
Authors: Boris Freidlin, Larissa A. Korde, Edward L. Korn
Journal: Journal of Clinical Oncology (2023)

Recent therapeutic advances have led to improved patient survival in many cancer settings. Although prolongation of survival remains the ultimate goal of cancer treatment, the availability of effective salvage therapies could make definitive phase III trials with primary overall survival (OS) end points difficult to complete in a timely manner. Therefore, to accelerate development of new therapies, many phase III trials of new cancer therapies are now designed with intermediate primary end points (eg, progression-free survival in the metastatic setting) with OS designated as a secondary end point. We review recently published phase III trials and assess contemporary practices for designing and reporting OS as a secondary end point. We then provide design and reporting recommendations for trials with OS as a secondary end point to safeguard OS data integrity and optimize access to the OS data for patient, clinician, and public-health stakeholders.
Effects of an urban cable car intervention on physical activity: the TrUST natural experiment in Bogotá, Colombia
Authors: Laura Baldovino-Chiquillo, Olga L Sarmiento, Gary O'Donovan, Maria A Wilches-Mogollon, Andres F Aguilar, Alberto Florez-Pregonero, Paola A Martínez, Julian Arellana, Luis A Guzmán, Goro Yamada, Daniel A Rodriguez, Ana V Diez-Roux
Journal: The Lancet Global Health (2023)
Recombinant Interleukin‐1 Receptor Antagonist Is an Effective <scp>First‐Line</scp> Treatment Strategy in <scp>New‐Onset</scp> Systemic Juvenile Idiopathic Arthritis, Irrespective of <scp>HLA‐DRB1</scp> Background and <scp><i>IL1RN</i></scp> Variants
Authors: Remco G. A. Erkens, Jorg J. A. Calis, Anouk Verwoerd, Sytze De Roock, Nienke M. Ter Haar, Gerda Den Engelsman, Lars T. Van der Veken, Robert F. Ernst, Hanneke W. M. Van Deutekom, Alex Pickering, Rianne C. Scholman, Marc H. A. Jansen, Joost F. Swart, Rashmi Sinha, Johannes Roth, Grant S. Schulert, Alexei A. Grom, Jorg Van Loosdregt, Sebastiaan J. Vastert
Journal: Arthritis & Rheumatology (2023)

Objective Human leukocyte antigen (HLA)‐DRB1*15:01 has been recently associated with interstitial lung disease (LD), eosinophilia, and drug reactions in systemic juvenile idiopathic arthritis (sJIA). Additionally, genetic variants in IL1RN have been linked to poor response to anakinra. We sought to reproduce these findings in a prospective cohort study of patients with new‐onset sJIA treated with anakinra as first‐line therapy. Methods HLA and IL1RN risk alleles were identified via whole‐genome sequencing. Treatment responses and complications were compared between carriers versus noncarriers. Results Seventeen of 65 patients (26%) carried HLA‐DRB1*15:01, comparable with the general population, and there was enrichment for HLA‐DRB1*11:01, a known risk locus for sJIA. The rates of clinical inactive disease (CID) at 6 months, 1 year, and 2 years were generally high, irrespective of HLA‐DRB1 or IL1RN variants, but significantly lower in carriers of an HLA‐DRB1*11:01 allele. One patient, an HLA‐DRB1*15:01 carrier, developed sJIA‐LD. Of the three patients with severe drug reactions to biologics, one carried HLA‐DRB1*15:01. The prevalence of eosinophilia did not significantly differ between HLA‐DRB1*15:01 carriers and noncarriers at disease onset (6.2% vs 14.9%, P = 0.67) nor after the start of anakinra (35.3% vs 37.5% in the first 2 years of disease). Conclusion We observed high rates of CID using anakinra as first‐line treatment irrespective of HLA‐DRB1 or IL1RN variants. Only one of the 17 HLA‐DRB1*15:01 carriers developed sJIA‐LD, and of the three patients with drug reactions to biologics, only one carried HLA‐DRB1*15:01. Although thorough monitoring for the development of drug hypersensitivity and refractory disease courses in sJIA, including sJIA‐LD, remains important, our data support the early start of biologic therapy in patients with new‐onset sJIA irrespective of HLA‐DRB1 background or IL1RN variants. image
Trends in the Prevalence of Hepatitis C Infection During Pregnancy and Maternal-Infant Outcomes in the US, 1998 to 2018
Authors: Po-Hung Chen, Lauren Johnson, Berkeley N. Limketkai, Emily Jusuf, Jing Sun, Brian Kim, Jennifer C. Price, Tinsay A. Woreta
Journal: JAMA Network Open (2023)

Importance Injection drug use is the primary risk factor for hepatitis C virus (HCV) infection in adults. More than one-third of newly reported HCV cases occur in women, particularly among persons aged 20 to 39 years. However, nationally representative data on HCV during pregnancy are limited. Objective To estimate the temporal trend of HCV-positive pregnancies during the opioid epidemic and identify HCV-associated maternal and perinatal outcomes. Design, Setting, and Participants A cross-sectional study was performed with data from the US, from calendar year 1998 through 2018. Data analysis was conducted from November 14, 2021, to May 14, 2023. Participants included women during in-hospital childbirth or spontaneous abortion in the National Inpatient Sample of the Healthcare Cost and Utilization Project. Exposure Maternal HCV infection. Main Outcomes and Measures The main outcome was the temporal trend, measured as change in the annual prevalence, in the prevalence of HCV positivity among pregnant women since the start of the opioid epidemic in the late 1990s. Secondary outcomes were the associations shown as relative odds between maternal HCV infection and maternal and perinatal adverse events. Results During the study period, more than 70 million hospital admissions resulted in childbirth or spontaneous abortion. Among them, 137 259 (0.20%; 95% CI, 0.19%-0.21%) involved mothers with HCV; these individuals were more often White (77.4%; 95% CI, 76.1%-78.6%), low-income (40.0%; 95% CI, 38.6%-41.5%), and likely to have histories of tobacco (41.7%; 95% CI, 40.6%-42.9%), alcohol (1.8%; 95% CI, 1.6%-2.0%), and opioid (28.9%; 95% CI, 27.3%-30.6%) use compared with HCV-negative mothers. The median age of women with HCV was 28.0 (IQR, 24.3-32.2) years, and the median age of HCV-negative women was 27.2 (IQR, 22.7-31.8) years. The prevalence of HCV-positive pregnancies increased 16-fold during the study period, reaching 5.3 (95% CI, 4.9-5.7) cases per 1000 pregnancies in 2018. Age-specific prevalence increases ranged from 3-fold (age, 41-50 years) to 31-fold (age, 21-30 years). Higher odds of cesarean delivery, preterm labor, poor fetal growth, or fetal distress were associated with HCV-positivity during pregnancy. However, no significant differences were observed in gestational diabetes, preeclampsia, eclampsia, or stillbirths. Conclusions and Relevance In this cross-sectional study, the prevalence of HCV-positive pregnancies increased markedly, and maternal HCV infection was associated with increased risks for adverse perinatal outcomes. These data may support recent recommendations for universal HCV screening with each pregnancy.
Are haematopoietic stem cell transplants stem cell transplants, is there a threshold dose of CD34-positive cells and how many are needed for rapid posttransplant granulocyte recovery?
Authors: Junren Chen, Robert Peter Gale, Yahui Feng, Yu Hu, Saibing Qi, Xueou Liu, Huaiping Zhu, Xiaowen Gong, Wei Zhang, Huilan Liu, Zimin Sun
Journal: Leukemia (2023)
Engineering Cardiac Tissue for Advanced Heart‐On‐A‐Chip Platforms
Authors: Xinyi Chen, Sitian Liu, Mingying Han, Meng Long, Ting Li, Lanlan Hu, Ling Wang, Wenhua Huang, Yaobin Wu
Journal: Advanced Healthcare Materials (2023)

Cardiovascular disease is a major cause of mortality worldwide, and current preclinical models including traditional animal models and 2D cell culture models have limitations in replicating human native heart physiology and response to drugs. Heart-on-a-chip (HoC) technology offers a promising solution by combining the advantages of cardiac tissue engineering and microfluidics to create in vitro 3D cardiac models, which can mimic key aspects of human microphysiological systems and provide controllable microenvironments. Herein, recent advances in HoC technologies are introduced, including engineered cardiac microtissue construction in vitro, microfluidic chip fabrication, microenvironmental stimulation, and real-time feedback systems. The development of cardiac tissue engineering methods is focused for 3D microtissue preparation, advanced strategies for HoC fabrication, and current applications of these platforms. Major challenges in HoC fabrication are discussed and the perspective on the potential for these platforms is provided to advance research and clinical applications.
An adaptive behavioral control motif mediated by cortical axo-axonic inhibition
Authors: Kanghoon Jung, Minhyeok Chang, André Steinecke, Benjamin Burke, Youngjin Choi, Yasuhiro Oisi, David Fitzpatrick, Hiroki Taniguchi, Hyung-Bae Kwon
Journal: Nature Neuroscience (2023)

Abstract Genetically defined subgroups of inhibitory interneurons are thought to play distinct roles in learning, but heterogeneity within these subgroups has limited our understanding of the scope and nature of their specific contributions. Here we reveal that the chandelier cell (ChC), an interneuron type that specializes in inhibiting the axon-initial segment (AIS) of pyramidal neurons, establishes cortical microcircuits for organizing neural coding through selective axo-axonic synaptic plasticity. We found that organized motor control is mediated by enhanced population coding of direction-tuned premotor neurons, with tuning refined through suppression of irrelevant neuronal activity. ChCs contribute to learning-dependent refinements by providing selective inhibitory control over individual pyramidal neurons rather than global suppression. Quantitative analysis of structural plasticity across axo-axonic synapses revealed that ChCs redistributed inhibitory weights to individual pyramidal neurons during learning. These results demonstrate an adaptive logic of the inhibitory circuit motif responsible for organizing distributed neural representations. Thus, ChCs permit efficient cortical computation in a targeted cell-specific manner.
Effects of sotatercept on lung diffusion capacity and blood gases in patients with pulmonary arterial hypertension
Authors: Karen M. Olsson, Jan Fuge, Da-Hee Park, Jan C. Kamp, Torben Brod, Britta Harrigfeld, Jonas C. Schupp, Marius M. Hoeper
Journal: European Respiratory Journal (2023)

Pulmonary arterial hypertension (PAH) is a rare disease characterised by remodelling of small pulmonary vessels, which results in a progressive increase in right ventricular afterload [1]. Most of the symptoms and signs of PAH are attributable to impaired right heart function. However, patients with PAH also show variable alterations of their lung diffusion capacity for carbon monoxide ( D LCO) and gas exchange, which contribute to disease symptoms and severity. Sotatercept may improve lung diffusion capacity for carbon monoxide and oxygenation in patients with pulmonary arterial hypertension <https://bit.ly/3PUUmjw> We are indebted to Susanne Tayler, Nicole Wintzenburg, Franziska Zetzsche, and Nicole Shearman (all from the Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany) for their invaluable support during the studies.
GAS6-based CAR-T cells exhibit potent antitumor activity against pancreatic cancer
Authors: Jiawei Fan, Ye Yu, Lanzhen Yan, Yuncang Yuan, Bin Sun, Dong Yang, Nan Liu, Jing Guo, Jie Zhang, Xudong Zhao
Journal: Journal of Hematology & Oncology (2023)

The receptor tyrosine kinases TAM family (TYRO3, AXL, and MERTK) are highly expressed in multiple forms of cancer cells and tumor-associated macrophages and promote the development of cancers including pancreatic tumor. Targeting TAM receptors could be a promising therapeutic option.We designed a novel CAR based on the extracellular domain of growth arrest-specific protein 6 (GAS6), a natural ligand for all TAM members. The ability of CAR-T to kill pancreatic cancer cells is tested in vitro and in vivo, and the safety is evaluated in mice and nonhuman primate.GAS6-CAR-T cells efficiently kill TAM-positive pancreatic cancer cell lines, gemcitabine-resistant cancer cells, and cancer stem-like cells in vitro. GAS6-CAR-T cells also significantly suppressed the growth of PANC1 xenografts and patient-derived xenografts in mice. Furthermore, these CAR-T cells did not induce obvious side effects in nonhuman primate or mice although the CAR was demonstrated to recognize mouse TAM.Our findings indicate that GAS6-CAR-T-cell therapy may be effective for pancreatic cancers with low toxicity.
Unique Spectrum of Activating<i>BRAF</i>Alterations in Prostate Cancer
Authors: Alex Chehrazi-Raffle, Hanna Tukachinsky, Eamon Toye, Smruthy Sivakumar, Alexa B. Schrock, Hannah E. Bergom, Hedyeh Ebrahimi, Sumanta Pal, Tanya Dorff, Neeraj Agarwal, Brandon A. Mahal, Geoffrey R. Oxnard, Justin Hwang, Emmanuel S. Antonarakis
Journal: Clinical Cancer Research (2023)

Alterations in BRAF have been reported in 3% to 5% of prostate cancer, although further characterization is lacking. Here, we describe the nature of BRAF alterations in prostate cancer using a large cohort from commercially available tissue and liquid biopsies subjected to comprehensive genomic profiling (CGP).Tissue and liquid biopsies from patients with prostate cancer were profiled using FoundationOne CDx and FoundationOne Liquid CDx CGP assays, respectively. Tissue biopsies from non-prostate cancer types were used for comparison (n = 275,151). Genetic ancestry was predicted using a single-nucleotide polymorphism (SNP) based approach.Among 15,864 tissue biopsies, BRAF-activating alterations were detected in 520 cases (3.3%). The majority (463 samples, 2.9%) harbored class II alterations, including BRAF rearrangements (243 samples, 1.5%), K601E (101 samples, 0.6%), and G469A (58 samples, 0.4%). BRAF-altered prostate cancers were enriched for CDK12 mutations (OR, 1.87; 9.2% vs. 5.2%; P = 0.018), but depleted in TMPRSS2 fusions (OR, 0.25; 11% vs. 32%; P < 0.0001), PTEN alterations (OR, 0.47; 17% vs. 31%; P < 0.0001), and APC alterations (OR, 0.48; 4.4% vs. 8.9%; P = 0.018) relative to BRAF wild-type (WT) disease. Compared with patients of European ancestry, BRAF alterations were more common in tumors from patients of African ancestry (5.1% vs. 2.9%, P < 0.0001) and Asian ancestry (6.0% vs. 2.9%, P < 0.001).Activating BRAF alterations were detected in approximately 3% of prostate cancers, and most were class II mutations and rearrangements; BRAF V600 mutations were exceedingly rare. These findings suggest that BRAF activation in prostate cancer is unique from other cancers and supports further clinical investigation of therapeutics targeting the mitogen-activated protein kinase (MAPK) pathway.
Confounding is a risk for all observational designs
Authors: Jennifer J. Lawrence
Journal: European Respiratory Journal (2023)

There are flaws to this analysis that threaten the claim of causality. The main one being the fact that many of the single nucleotide polymorphisms used to instrument GORD are strongly associated with body composition. There is no causal relationship between gastro-oesophageal reflux disease and idiopathic pulmonary fibrosis https://bit.ly/3BD0hBb
CPAP therapy for obstructive sleep apnoea: are the right questions being asked?
Authors: Daniel J. Gottlieb
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>The AHRQ assessment of the impact of CPAP on long-term health outcomes in sleep apnoea is flawed in its failure to consider the impact of CPAP on sleepiness, but correctly identifies a lack of clinic trial evidence of cardiovascular benefits from CPAP</b>https://bit.ly/3D5Ekf3
mRNA vaccine against malaria tailored for liver-resident memory T cells
Authors: Mitch Ganley, Lauren E. Holz, Jordan J. Minnell, Maria N. de Menezes, Olivia K. Burn, Kean Chan Yew Poa, Sarah L. Draper, Kieran English, Susanna T. S. Chan, Regan J. Anderson, Benjamin J. Compton, Andrew J. Marshall, Anton Cozijnsen, Yu Cheng Chua, Zhengyu Ge, Kathryn J. Farrand, John C. Mamum, Calvin Xu, Ian A. Cockburn, Katsuyuki Yui, Patrick Bertolino, Stephanie Gras, Jérôme Le Nours, Jamie Rossjohn, Daniel Fernandez-Ruiz, Geoffrey I. McFadden, David F. Ackerley, Gavin F. Painter, Ian F. Hermans, William R. Heath
Journal: Nature Immunology (2023)